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  3. PON1

PON1 (Paraoxonase 1)

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Summary of PON1

PON1 is responsible for detoxifying organophosphate pesticides, nerve gasses and various drugs (R). PON1 has a role in healthy ageing (R) and helps protect against bacterial infection (R), heart disease (R), stroke, diabetes, liver and kidney diseases, arthritis, eye diseases (macular degeneration), cancer and HIV infection (R). People with Autism have lower PON1 activity (arylesterase activity) (R).  

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The Function of PON1

Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation.

Protein names

Recommended name:

Serum paraoxonase/arylesterase 1

Short name:

K-45

Alternative name(s):

PON 1
Aromatic esterase 1
A-esterase 1
Serum aryldialkylphosphatase 1

PON1 SNPs

    To see your genotype, you should be logged in and have a file with your genotype uploaded.

  1. RS2057681 (PON1) ??
  2. RS3735590 (PON1) ??
  3. RS4242382 (PON1) ??
  4. RS662 (PON1) ??
  5. RS705379 (PON1) ??
  6. RS705381 (PON1) ??
  7. RS854555 (PON1) ??
  8. RS854560 (PON1) ??
  9. RS854571 (PON1) ??
  10. RS854572 (PON1) ??

Top Gene-Substance Interactions

PON1 Interacts with These Diseases

Disease Score

Fixes

How to increase PON1:

  • Vitamin E
  • Mediterranean Diet (R),
  • Extra Virgin Olive Oil (R),
  • Fish oil/DHA (R, R2),
  • Broccoli sprouts/Sulforaphane (Ref),
  • Allyl isothiocyanate (found in mustard, radish, wasabi) (R)
  • Curcumin (R),

Mitigate things that decrease PON1: 

  • Omega-6s such as linolenic acid and arachidonic acid decrease PON1 (R).
  • Low grade inflammation will decrease PON1, so you should fix general inflammation (R).
  • PON1 in human blood is inactivated by oxidized LDL and preserved by antioxidants (R), so taking care of oxidative stress in general is a good idea.

Fixes Advanced

Activating PPAR gamma increases the synthesis and release of PON1 from the liver (R).

Other ways to increase PON1:

  • Vitamin E
  • Mediterranean Diet (R),
  • Extra Virgin Olive Oil (R),
  • Fish oil/DHA (R, R2),
  • Broccoli sprouts/Sulforaphane (Ref),
  • Allyl isothiocyanate (found in mustard, radish, wasabi) (R)
  • Curcumin (R),
  • EGCG (R),
  • Aspirin  (R)
  • Quercetin (R),
  • Pomegranate (R),
  • Resveratrol (R),
  • Berberine (R)
  • Glutathione (R),
  • Statins (R)
  • Other: Sumac (R), Atorvastatin (R),

Other: Bile acids inhibit PON1 via FXR activation (R)

Substances That Increase PON1

Substances Interaction Organism Category

Substances That Decrease PON1

Substances Interaction Organism Category

Advanced Summary

Read  PON1: It's Critical Function in Preventing Heart Disease and Natural Ways to Increase It.

PON1 is responsible for detoxifying organophosphate pesticides and nerve gasses. It detoxifies lactones (such as statins), glucuronide drugs, thiolactones, aryl esters, cyclic carbonates, estrogens and lipid peroxides (oxidised lipids) (R).

PON1 also protects against bacterial infection by destroying the bacterial signaling molecules that cause gram-negative bacteria to invade human tissue and form colonies, thus PON1 contributes to the bodies innate immunity (R).

PON1 (paraoxonase 1) is a major anti-atherosclerotic component of HDL.  PON1 is transported by HDL, which is one significant reason (if not the only reason) why having higher HDL is protective against heart disease (R). It protects against the induction of inflammatory responses in artery wall cells by destroying biologically active lipids in oxidized LDL (R).

Oxidized-fats and cholesterol are the major cause of inflammation and are responsible for the initiation and/or propagation of several inflammatory diseases including heart disease and stroke, diabetes, liver and kidney diseases, arthritis, eye diseases (macular degeneration), cancer and HIV infection (R).

Because of its ability to destroy oxidised-lipids, PON1 appears to play some role in all these diseases. However, the greatest research interest has been the role of PON1 in heart disease, because of its ability to remove harmful oxidized-lipids (R).

  PON1 has a role in healthy ageing (R). People with Autism have lower PON1 activity (arylesterase activity) (R). PON1 increases SIRT1  (R).

     From NCBI Gene: Microvascular complications of diabetes 5From UniProt: Microvascular complications of diabetes 5 (MVCD5): Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. [MIM:612633]

     From NCBI Gene: The enzyme encoded by this gene is an arylesterase that mainly hydrolyzes paroxon to produce p-nitrophenol. Paroxon is an organophosphorus anticholinesterase compound that is produced in vivo by oxidation of the insecticide parathion. Polymorphisms in this gene are a risk factor in coronary artery disease. The gene is found in a cluster of three related paraoxonase genes at 7q21.3. [provided by RefSeq, Oct 2008] From UniProt: Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification and the consequent series of events leading to atheroma formation.

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • GR
  • GR-alpha
  • GR-beta
  • p53
  • Sp1

Tissue specificity:

Plasma, associated with HDL (at protein level). Expressed in liver, but not in heart, brain, placenta, lung, skeletal muscle, kidney or pancreas.

Gene Pathways:

  • Metabolic pathways

Cofactor:

Binds 2 calcium ions per subunit.

Molecular Function:

  • Acyl-L-Homoserine-Lactone Lactonohydrolase Activity
  • Aryldialkylphosphatase Activity
  • Arylesterase Activity
  • Calcium Ion Binding
  • Phospholipid Binding
  • Protein Homodimerization Activity

Biological Processes:

  • Aromatic Compound Catabolic Process
  • Carboxylic Acid Catabolic Process
  • Cholesterol Metabolic Process
  • Organophosphate Catabolic Process
  • Phosphatidylcholine Metabolic Process
  • Positive Regulation Of Binding
  • Positive Regulation Of Cholesterol Efflux
  • Positive Regulation Of Transporter Activity
  • Response To External Stimulus
  • Response To Fatty Acid
  • Response To Fluoride
  • Response To Nutrient Levels
  • Response To Toxic Substance

Drug Bank:

  • Cefazolin
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

hypothetical protein| ESA| A-esterase 1| aromatic esterase 1| arylesterase 1| arylesterase B-type| EGK_13925| esterase A| H920_14696| K-45| MVCD5| PAL_GLEAN10021748| PANDA_007528| paraoxonase B-type| PON| PON 1| serum aryldiakylphosphatase| serum aryldialkylphosphatase 1| serum paraoxonase| serum paraoxonase/arylesterase 1| TREES_T100012330| pon1

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